title: In situ forming hydrogels via catalyst-free and bioorthogonal "tetrazole-alkene" photo-click chemistry.
abstract: In situ forming hydrogels were developed from 4-arm poly(ethylene glycol)-methacrylate (PEG-4-MA) and -tetrazole (PEG-4-Tet) derivatives through catalyst-free and bioorthogonal "tetrazole-alkene" photo-click chemistry. PEG-4-MA and PEG-4-Tet (Mn = 10 kg/mol) were soluble at 37 °C in phosphate buffer (PB, pH 7.4, 10 mM) at total polymer concentrations ranging from 20 to 60 wt % but formed fluorescent hydrogels upon 365 nm UV irradiation at an intensity of 20.6, 30.7, or 60 mW/cm(2). The gelation times ranged from ca. 50 s to 5 min, and storage moduli varied from 0.65 to 25.2 kPa depending on polymer concentrations and degrees of Tet substitution in PEG-4-Tet conjugates. The cell experiments via an indirect contact assay demonstrated that these "tetrazole-alkene" photo-click PEG hydrogels were noncytotoxic. The high specificity of photo-click reaction renders thus obtained PEG hydrogels particularly interesting for controlled protein release. Notably, in vitro release studies showed that cytochrome c (CC), γ-globulins (Ig), and recombinant human interleukin-2 (rhIL-2) all were released from PEG hydrogels in a sustained and quantitative manner over a period of 14-20 days. Importantly, released CC and rhIL-2 exhibited comparable biological activities to native CC and rhIL-2, respectively. These results confirm that "tetrazole-alkene" photo-click reaction is highly compatible with these loaded proteins. This photo-controlled, specific, efficient, and catalyst-free click chemistry provides a new and versatile strategy to in situ forming hydrogels that hold tremendous potentials for protein delivery and tissue engineering.
authors.affiliation: Biomedical Polymers Laboratory, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, People's Republic of China.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Fan
authors.forename: Chao
authors.initials: C
authors.lastname: Deng
authors.forename: Ru
authors.initials: R
authors.lastname: Cheng
authors.forename: Fenghua
authors.initials: F
authors.lastname: Meng
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Zhong
mesh_terms: D000475:Alkenes / Q000737:chemistry; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D002384:Catalysis; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D057930:Click Chemistry; D045304:Cytochromes c / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000138:chemical synthesis / Q000633:toxicity; D006801:Humans; D020100:Hydrogels / Q000138:chemical synthesis* / Q000633:toxicity; D007376:Interleukin-2 / Q000737:chemistry / Q000494:pharmacology; D007700:Kinetics; D051379:Mice; D044367:Phase Transition; D055668:Photochemical Processes; D011092:Polyethylene Glycols / Q000737:chemistry*; D013777:Tetrazoles / Q000737:chemistry*; D005719:gamma-Globulins / Q000737:chemistry
chemical_list: D000475:Alkenes; D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D020100:Hydrogels; D007376:Interleukin-2; D013777:Tetrazoles; D005719:gamma-Globulins; D011092:Polyethylene Glycols; D045304:Cytochromes c